Previous studies indicated that almost one-third of the curatively resected PDAC patients would experience a local relapse, but without distant metastases [26, 27]. The rationale underlying the RT combination involves decreasing of the local relapse, which possesses the same lethality as that of distant metastasis. However, the true impact of RT still remains questionable. Based on the PSM analysis, the current study investigated the survival outcomes between patients undergoing postoperative RT after surgery and patients who underwent surgery alone for resectable pancreatic head cancer.
The treatment process of patients undergoing postoperative RT in the surgery group and the surgery-alone group was shown in Figs. 2 and 3. In baseline cohort and matched cohort, the median OS of patients in the postoperative RT group was longer than that of patients in the surgery-alone group.. Although there were fewer patients in the postoperative RT group who underwent surgical resection than in the surgery-alone group, the results showed that patients with resectable pancreatic head cancer with postoperative RT therapy obtained a survival advantage over those who have undergone surgery alone. Subset analyses revealed that this benefit was restricted to patients with Lymph node invasion. Patients without lymph node invasion already had a relatively impressive median survival of 31 months, and post-operative RT was not associated with additional benefit in this group. As such, these data highlight the need for more intensive study of the potential benefit of RT in the multidisciplinary treatment of pancreatic head adenocarcinoma.
The survival benefit of adjuvant postoperative RT was first revealed in the Gastrointestinal Tumor Study Group (GITSG) 9173 study . However, A meta-analysis investigated 15 clinical trials and reported that adjuvant postoperative RT could not improve disease-free survival (DFS), 2-year survival, or OS when compared to those with surgery alone, but adjuvant CT could improve all the three outcomes . Another multi-center study analyzed 955 patients who underwent pancreatic cancer resections and concluded that adjuvant postoperative RT with CT improved patient’s survival as compared to CT alone . However, Morak et al. have suggested that neoadjuvant chemo(radio)therapy following resection showed no benefit in the OS of patients . However, these trials lacked quality control of RT and had a selection bias. The ESPAC-1 study demonstrated that RT combined with adjuvant 5-FU CT might be redundant or even harmful . Several concerns have been put forward about this trial criticizing their lack of attention to quality control for RT [33–35]
However, our large study, while still retrospective, used robust methods to avoid treatment selection bias, demonstrating survival benefit with adjuvant postoperative RT. Our study included patients who underwent treatment in the “real-world” setting as compared to the highly selected patients included in the clinical trials. Patients with adenocarcinoma histology and receiving the Whipple procedure were only included. To improve the reliability of the research, patients who received CT were excluded. The benefit of radiation was observed by conducting univariate and multivariate analyses. The radiation techniques have improved over time with more precise delivery to maximize the dose to the target tumor and minimize the dose to the normal tissues, daily integration of imaging before each fraction of the treatment, and identification of the variation in tumor position of the pancreatic tumor with respiration .
However, our study has several limitations. First, despite the use of PSM to address treatment selection bias, the potential for a residual bias still remained in this retrospective cohort study. Second, the adverse effects induced by the treatments cannot be addressed, and thus, the mortality estimation drawn based on such treatment might be biased. Also, the increased survival rates of the postoperative RT group in the present study might be underestimated. Third, the serum tumor marker of CA 19 − 9 that is associated with poor prognosis in patients with advanced PA receiving systemic CT [43,44] was absent in our study. Yet, whether the CA19-9 itself is considered to be vital in determining the survival in PDAC patients receiving postoperative RT remains controversial. Fourth, dietary habits, socioeconomic status and body mass index, which might be the risk factors of mortality, were absent from the SEER database. Fifth, the SEER database did not include information on arterial or venous tumors involved or the presence of borderline resectable lesions. Therefore, we limited to using clinical stages. Sixth, the SEER database lacked the information regarding RT agents and the doses and combinations used, and therefore no specific recommendations could be drawn with respect to a specific RT protocol. Finally, we were unable to adopt the heterogeneity in the delivered treatment regimens, which were not available in the SEER database. Finally, as SEER did not include data on recurrence patterns, we could only speculate as to whether improved survival is associated with local or systemic disease control.